Heterocyclic phenols



.Patented Mar. 29, 1938 I i 2,112,

UNITED STATES PATENT OFFICE HETEROCYCLIC PHENOLS Joseph B. Niederl, New York, N. Y.

No Drawing. Application March 24, 1936,

Serial No. 70,613

1 Claims. (01. 260-44) This invention relates to a new class of chemiphenol having a free reactive nuclear position 'cal compounds and to a process by which they available for condensation.

can be prepared. More specifically, it relates to By the expression "p-ethylenic lsocyanate I oxazoline and thiazoline phenols that are preintend to include compounds of the general for- 5 pared by condensing ethylenic isocyanates or iscmula RaC QR-CRz-NCO wherein the R's are 5 thiocyanates with phenols in thepresence of a similar or diflerent and may be hydrogen or a cationoid condensing agent. saturated alkyl or cycloalkyl group. The expres- It has heretofore been known that unsaturated slon "p ethylenic isothiocyanates is intended to aliphatic hydrocarbons can be condensed with include the corresponding group of isothiocyphenols to produce alkyl substituted phenols. anates. 10 Such a process is disclosed in my prior Patent The expression "cationoid condensing agent is 2,008,032 granted July 16, 1935. I have now used herein in the sense of the recent electronic found that when ethylenlc isocyanates or isothio postulations of Robert Robinson; compare for v cyanates are condensed with phenols the con instance his book on Versuch einer Elektronenl5 densation takes place not at the ethylenic group theorie organisoh-chemischer Reaktionen", Veras would be expected, but in the cyanate radical lag Ferdinand Enke,- Stuttgart 1932., especially and is followed by a ring closure that forms an page 16. Such agents are protons and sources oxazoline or thlazolinc group. Thus, according oi p'rotons,such as acids, or metal atoms which to this invention, compounds oi. the structural are able to form ctiordination systems with water formula or ammonia, or atoms and free radicals with in- 20 R complete electron shells. Especially suitable have been found the following agents: sulphuric EAMLOH I acid, hydrochloric acid, hydrobromic acid, phosphoric acid, zinc chloride, aluminum chloride,

boron trifluoride, copper chloride, and other cationoid agents. They do not enter into reaction with the above mentioned reaction compounds but remain unchanged and act, thus, catalytically.

25 are produced by condensing an unsaturated alkylene isocyanate with phenol. Where an unsaturated alkyl isothiocyanate is used, compounds of the general formula 39 R The following examples are given as specific R,cncs' illustrations of how my invention may be carried J h-cm on out and should not be construed as limitations In N thereupon: are produced. Example 1.-Allyl isocyanate and phenol-To 5 In practicing this invention molecular equivaa molar mixture of allyl isocyanate and phenol lent quantities of a phenol and an ethylenic isonot more than one mol. equivalent of cone. sulcyanate or isothiocyanate are mixed and to the phuric acid is added, the temperature of the remixture approximately one molecular equivalent action mixture being kept between 0-5 C. After of a cationoid condensing agent is slowly added the addition of the acid the mixture is allowed to '40 while the reaction mass is thoroughly agitated stand for several days until the reaction is com- 40 and cooled to a temperature in the neighborhood plete. The condensed material is then extracted of- 0 C. After all the condensing agent is added, with water to remove any and all water soluble, the mixture is allowed to stand for one or more as well as acid soluble, material. This extract days until the reaction is complete. The new is then neutralized with sodium carbonate or condensation products can be separated from the sodium hydroxide. The oxazolinephenol sep- 45 reaction mass by extracting with a small amount arates as an oil which is then dissolved in ethyl of water and are recovered from the extracting acetate and dried over anhydrous calcium chlosolution by neutralizing with alkali hydroxide or ride. The extract-is then filtered and the ethyl carbonate. Further purification can be effected acetate, together with the lower distilling startby extracting the recovered condensation product lng materials as well as by-products, is removed 50 with an organic solvent and removing the solvent by distillation under diminished pressure. The and other volatile materials by vacuum distillaresidue is once more dissolved in ethyl acetate tion. By this method oxazoline and thiazoline or any other non-reactive organic solvent and phenols can be prepared by condensing any 5- this extract is treated with dilute hydrochloric ethylenic isocyanate or isothiocyanate with any acid (10%) and the acidic aqueous extract is. 55v

again separated. This acidic extract is then flltered and carefully neutralized with sodium hydroxide or carbonate. The oxazolinephenol first separates out in form of finely divided oilythe entire addition of the condensing agent, but

also for the next 24 hours, after which, the reaction mixture is left standing for 3 days at room temperature to bring the reaction to completion. The condensation product is then treated with small amounts of water to extract the sulphuric acid as well as all acid soluble material. This aqueous extract is neutralized with sodium carbonate or sodium hydroxide and extracted exhaustively with ethyl acetate. The ethyl acetate extract is dried with anhydrous calcium chloride and filtered. The solvent, as well as most of the unreacted phenol, mustard oil and some allyl amine, are distilled off successively by gradually heating the condensation product to /10 mm. The remaining residue is once more dissolved in ethyl acetate and this solution extracted with dilute hydrochloric acid (10%). The acidic aqueous extract obtained is neutralized with sodium hydroxide or carbonate and the separating oil usually crystallizes on standing, otherwise it is once more taken up in ethyl acetate. Again the solvent is removed by vacuum distillation and the residue dissolved in a minimum of 95% ethyl alcohol. On prolonged standing of this concentrated alcoholic solution at about 0 C. the respective phenolic condensation products crystallize. Recrystallization is effected by using ethyl alcohol or benzene, together with Norite for the removal of highly colored impurities.

Another way to crystallize these condensation products is by dissolving the acid soluble oil as obtained above, in a minimum amount of aqueous sodium or potassium hydroxide. The resulting aqueous alkaline solution is filtered and then neutralized exactly with sulfuric or hydrochlpric acid. From this absolutely neutral solution, on standing, the thiazolinephenol first comes down in form of fine droplets and the entire mixture assumes a milky appearance. On further standing the thiazolinephenol thus precipitated, be-

comes crystalline. It is filtered OE, and recrystallized as described before.

In similar manners any phenol having a nuclear position (ortho or para) available for'reaction, such as the cresols, the xylenols, thymol,

carvacrol, p-cliisobutyl phenol, guaiacol, catechol,

tion of acetone until decided turbidity is ob- 1 served. The corresponding picrates are obtained by the slow addition of the filtered aqueous solutions of the hydrochlorides to an equal volume of a filtered concentrated aqueous solution of plcric acid. They can be recrystallized from 95% ethyl alcohol.

Allyl mustard oil yields specifically:

(a) With phenol: 5-methyl-2-(4'-hydroxy)- phenyl thiazoline (CioHuOSN), M. P.: 166-168 C.: hydrochloride (CmHuOSNCl), M. P.: 187 C.: picrate (CmI-IuOaSNO, M. P.: 178 C.

(b) With m-cresol: 5-methyl-2-(2'-methyl-4'- hydroxy) -phenyl thiazoline (CriHrsOSN), M. P.: 131 C.: hydrochloride (CnHmOSNCl), C.: picrate (Ci'IHiBOBSNL), M. P.: 154 C.

(a) With p-diisobutylphenol: 5-methyl-2-(2'- hydroxy-5-(a, a, 'y, y-tetramethyl) butyD-phenyl thiazoline (CmHz-IOSN).

(d) With guaiacol: 5-methyl-2-(4-hydroxy- 3'-methoxy) -phenyl thiazoline (CnHmOzSN), M. P.: 142 C.: hydrochloride (C11H14O2SNC1), M. P.: 187 C.: picrate (CirHisOsSN), M. P.: 159-160 C.

(e) With resorcinol: 5-methyl-2-(2' 4'-dihydroxy)-phenyl thiazoline (CmHnOzSN), M. P.: 184 C.: hydrochloride (CroHuOzSNCl), M. P.: 251 C.: picrate (C16H14O9SN4), M. P.: C.

Oxydative degradation of the above thiazoline phenols yield first the corresponding phenolic heterocyclic sulfoxides then the corresponding phenolic heterocyclic sulfones then the corresponding taurins (HO.02S.CH(CH3) CH2N=C.CsR4OH) or taurin amides (HO.O3S.CH(CH3) CHZNHOC-CBRAOH) and finally fl-methyl taurin. At the same time the phenolic radical is oxidized first to the corresponding phenolic aldehyde and then to the corresponding phenolic acid. In this way vanillin is obtained by oxidizing the thiazoline guaiacol compound.

As in the previous examples, the above process is not at all limited to the above mentioned specific examples, but any phenolic compound as well as any unsaturated isocyanate (yielding oxazoline phenols) or isothiocyanate may be used. For technical production of these thiazceutical values and at the same time are important azo dye stuff intermediates.

What I claim as my' invention is:

1. A process which consists in treating a phenol having at least one tree nuclear position available for condensation, with reacting proportions of a B-ethylenic isothiocyanate in the presence of an acidic catalyst as a condensing agent.

2. A process which consists in treating a phenol having at least one nuclear position available for condensation with reacting proportions of a j3-ethylenic isothiocyanate in the presence of sulphuric acid.

3. A process which consists in treating a phenol having at least one nuclear position-available for condensation with reacting proportions of allyl isothiocyanate in the presence of sulphuric acid.

4. As a new compound 5-methyl-2-(4'-hydroxy)-phenyl thiazoline.

5. Compounds of the general formula R R-c-s c-R'oH R-'--N R in which R represents a member of the group consisting of hydrogen and hydrocarbon radicals, nd R represents an aromatic nucleus.

6. As a new compound, 5-methyl-2-(2'-methy1- 4' -hydroxy phenyl) -thiazoline.

7. As a new compound, 5-methyl-2-(2',4*-dihydroxy phenyl) -thiazoline.

JOSEPH B. NIEDERL. 

